This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The heavy metal cadmium, a widespread environmental contaminant and component in cigarettes, accumulates in the body and poses a threat to human health. Bone is a critical target site for cadmium and human exposure to cadmium is linked to bone diseases, including osteoporosis and osteopenia. In 2005, a CDC report listed cadmium as a toxin that merits monitoring. This report, combined with the escalating cost of healthcare for osteoporosis, emphasizes the importance of research to decipher the underlying mechanisms of cadmium-induced osteotoxicity. Despite its recognized importance as an environmental toxin, little is known about how cadmium directly impacts bone cells, in particular the bone-forming osteoblasts. Research from our laboratory indicates that cadmium exposure induces apoptosis, programmed cell death, in osteoblastic cells. Our overarching research goal is to identify the intracellular mechanisms involved in cadmium-induced osteoblast apoptosis, which in turn, may ultimately contribute to net bone loss. Collectively, a cadmium osteotoxicity in vitro model may help identify targets for treatment and prevention of osteoporosis, a major metabolic bone disease with an annual cost 20 billion dollars.